Reversible stimuli-responsive nanomaterials with on-off switching ability for biomedical applications

Many long-acting extended drug release systems can provide controlled or sustained release of therapeutic payloads. In the majority of those systems drug release cannot be stopped once it has started because they operate autonomously regardless of the evolution of the treatment and/or the patient ' s needs. However, in several pathologies such as diabetes, hormonal disorders, pain management, etc. a pulsatile drug release is required to adjust the dose of drug release to the specific needs in a spatio-temporal manner. Additionally, in other pathologies such as cancer or antimicrobial therapy the release of the drug with spatio-temporal control to prevent unwanted side effects represents an unmet need. With this aim reversible stimuli-responsive nanomaterials with an on-off switching ability have been developed in order to provide a spatio-temporal control of the drug released. Those systems can be activated in response to exogenous (light, magnetic field, electrical fields, etc.) or endogenous triggers (pH, enzyme-substrate complex formation, protein-cell binding, etc.) thanks to the use of reversible phase-transition materials. In this review we compile in vitro and preclinical results in which those materials have been successfully used. The types of stimuli used to trigger drug release as well as the different nanomaterials used are reviewed in order to provide a general overview of the field. We anticipate that further studies in this field will be expanded towards the development of multimodal hybrid systems which combine therapy and imaging while reporting the evolution of the treatment in real time.